A retrospective study of 404 allogeneic hematopoietic stem cell transplant (HSCT) patients by the Fred Hutch Cancer Research Center at the University of Washington found that reactivation of a higher number of double stranded DNA (dsDNA) viruses (CMV, BKV, HHV-6B, EBV, and adenovirus) significantly increased the risk of overall mortality, as did an increased quantitative burden of viral exposure. In a model in which each virus was independently considered while adjusting for the presence of other viruses, HHV-6B conferred a significantly increased risk for overall mortality (see figure).

In this study, 90% of the patients had more than one dsDNA virus detected in plasma, 62% had 2 or more, and 28% had three or more. The highest risk of mortality appeared to correlate with patients who had reactivated HHV-6B, EBV, BKV, and CMV. The authors point out that absence of approved antiviral treatment for dsDNA viruses such as HHV-6, EBV, and adenovirus have limited their antiviral prevention strategies.

The rate of HHV-6 viremia was lower and the CMV rate was higher than what was found in a similar, Japanese study in 2015 that found 60% positivity for HHV-6 and only 10.5% each for CMV and EBV. The Fred Hutch group found that CMV viremia was the most common at 65% compared to 46% for HHV-6B, 10% for adenovirus, and 9% for EBV (Inazawa 2015). The high rate of CMV viremia may be in part due to the fact that the donor or recipient were CMV seropositive in 86% of selected patients, as well as other differences in HCT type and characteristics.

The authors point out that tissue injury by viruses may be underappreciated or misattributed to other causes. HHV-6, for example, can be active in the lung, liver, or heart tissue with little or no trace in the plasma. Only 34 (8.4%) end organ disease events and 8 deaths were clinically attributed to these dsDNA viruses.

The authors also note that viremia by dsDNA viruses may have indirect effects due to increased production of pro-inflammatory and immunomodulatory cytokines, and that viremia has been associated with an increased risk of bacterial and fungal infections, prolonged hospitalization, and death.

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ABOUT THE HHV-6 FOUNDATION

The HHV-6 Foundation in a non-profit entity founded to encourage scientific exchange between investigators and to provide pilot grants for promising scientific and clinical research on the under- appreciated viruses HHV-6A and HHV-6B.

The Foundation sponsors international conferences and supports scientists and clinicians seeking to clarify the role of the two HHV-6 viruses in disease. Since HHV-6A and HHV-6B can smolder in the brain and other organs without circulating in the peripheral blood or plasma, identifying chronic infection is a challenge.